Abstract
Quantitative-structure-toxicity-relationship (QSTR) models are developed for predicting the toxicity (pIGC50) of 252 aliphatic compounds on Tetrahymena pyriformis. The single parameter models with a simple molecular descriptor, the number of atoms in the molecule, provide reasonable results. Better QSTR models with two parameters result when global electrophilicity is used as the second descriptor. In order to tackle both charge-and frontier-controlled reactions the importance of the local electro (nucleo) philicities and atomic charges is also analysed.
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Smeyers Y G, Bouniam L, Smeyers N J, Ezzamarty A, Hernandez-Laguna A and Sainz-Diaz C I 1998 Eur. J. Med. Chem. 33 103
Busse W D, Ganellin C R and Mitscher L A 1996 Eur. J. Med. Chem. 31 747
Hansch C, Hoekman D, Leo A, Weininger D and Selassie C 2002 Chem. Rev. 102 783
Hansch C, Kurup A, Garg R and Gao H 2001 Chem. Rev. 101 619
Hansch C, Maloney P P, Fujita T and Muir R M 1962 Nature (London) 194 178
Hansch C, Li R I, Blaney J M and Langridge R J 1982 J. Med. Chem. 25 777
Leach A R and Gillet V J 2003 An introduction to chemoinformatics (Kluwer: Dordrecht)
Ormerod A, Willett P and Bawden D 1989 Quant. Struct-Act. Relat. 8 115
Akers K S, Sinks G D and Schultz T W 1999 Environ. Toxicol. Pharmacol. 7 33
Schultz T W 1997 Toxicol. Methods 7 289. TETRATOX database; http://www.vet.utk.edu/TETRATOX/
Dimitrov S D, Mekenyan O G, Sinks G D and Schultz T W 2003 J. Mol. Struct. (THEOCHEM) 622 63
Netzeva T I, Schultz T W, Aptula A O and Cronin M T D 2003 SAR QSAR Environ. Res. 14 265
Schultz T W, Cronin M T D, Netzeva T I and Aptula A O 2002 Chem. Res. Tox. 15 1602
Cronin M T D, Manga N, Seward J R, Sinks G D and Schultz T W 2001 Chem. Res. Tox. 14 1498
Xue Y, Li H, Ung C Y, Yap C W and Chen Y Z 2006 Chem. Res. Tox. 19 1030
Toropov A A and Benfenati E 2004 J. Mol. Struct. (THEOCHEM) 679 225; (b) Castro E A, Toropov A A, Nesterova A I and Nazarov A U 2003 J. Mol. Struct. (THEOCHEM) 639 129
Parr R G and Yang W 1989 Density functional theory of atoms and molecules (Oxford, UK: Oxford University Press); (b) Chattaraj P K (ed.) 2005 Special issue on chemical reactivity J. Chem. Sci. 117; (c) Geerlings P, De Proft F and Langenaeker W 2003 Chem. Rev. 103 1793
Chattaraj P K, Nath S and Maiti B 2004 Reactivity descriptors in computational medicinal chemistry for drug discovery (eds) J Tollenaere, P Bultinck, H D Winter and W Langenaeker (New York: Marcel Dekker) Chapter 11, p 295
Parthasarthi R, Subramanian V, Roy D R and Chattaraj P K 2004 Bioorg. Med. Chem. 12 5533
Roy D R, Parthasarathi R, Maiti B, Subramanian V and Chattaraj P K 2005 Bioorg. Med. Chem. 13 3405
Parthasarathi R, Elango M, Padmanabhan J, Subramanian V, Roy D R, Sarkar U and Chattaraj P K 2006 Indian J. Chem. A 45 111
Parthasarathi R, Padmanabhan J, Subramanian V, Maiti B and Chattaraj P K 2004 Curr. Sci. 86 535
Sarkar U, Roy D R, Chattaraj P K, Parthasarathi R, Padmanabhan J and Subramanian V 2005 J. Chem. Sci. 117 599
Padmanabhan J, Parthasarathi R, Subramanian V and Chattaraj P K 2006 Chem. Res. Tox. 19 356
Roy D R, Parthasarathi R, Padmanabhan J, Sarkar U, Subramanian V and Chattaraj P K 2006 J. Phys. Chem. A 110 1084.
Parthasarathi R, Padmanabhan J, Subramanian V, Maiti B and Chattaraj P K 2003 J. Phys. Chem. A 107 10346
Padmanabhan J, Parthasarathi R, Subramanian V and Chattaraj P K 2005 J. Phys. Chem. A 109 11043
Padmanabhan J, Parthasarathi R, Subramanian V and Chattaraj P K 2006 J. Phys. Chem. A 110 2739
Roy D R, Sarkar U, Chattaraj P K, Mitra A, Padmanabhan J, Parthasarathi R, Subramanian V, Vandamme S and Bultinck P 2006 Mol. Div. 10 119
Roy D R, Parthasarathi R, Subramanian V and Chattaraj P K 2006 QSAR & Comb. Sci. 25 114
Parr R G, Szentpaly L V and Liu S 1999 J. Am. Chem. Soc. 121 1922
Chattaraj P K, Sarkar U and Roy D R 2006 Chem. Rev. 106 2065; (b) Chattaraj P K and Roy D R 2007 Chem. Rev. 107 PR46
Chattaraj P K, Maiti B and Sarkar U 2003 J. Phys. Chem. A 107 4973
Szymanski V, Müller W R, Knop J V and Trinajstić N 1986 Int. J. Quantum Chem. 30 173; (b) Roy D R, Pal N, Mitra A, Bultinck P, Parthasarathi R, Subramanian V and Chattaraj P K 2007 Eur. J. Med. Chem. Doi:10:10.1016/j.ejmech.2007.01.028; (c) Giri S, Roy D R, Bultinck P, Subramanian V and Chattaraj P K 2007 QSAR Comb. Sci. (in press)
Yang W and Mortier W J 1986 J. Am. Chem. Soc. 108 5708
Klopman G (ed.) 1974 Chemical reactivity and reaction paths (New York: Wiley); Klopman G 1968 J. Am. Chem. Soc. 90 223
Chattaraj P K 2001 J. Phys. Chem. A 105 511
Melin J, Aparicio F, Subramanian V, Galvan M and Chattaraj P K 2004 J. Phys. Chem. A 108 2487
Gaussian 03, Revision B.03; Pittsburgh, PA: Gaussian, Inc.
Livingstone D J and Salt D W 2006 Rev. Comput. Chem. 21 287
Whitley D, Ford M G and Livingstone D J 2004 J. Chem. Inf. Comp. Sci. 40 1160
Van Damme S and Bultinck P 2007 J. Comp. Chem. 28 1924
Hawkins D M, Basak S C and Mills D 2003 J. Chem. Inf. Comput. Sci. 43 579
Principle of Parsimony: All things being approximately equal, one should accept the simplest possible model (Occam’s Razor; William of Ockham, 1285–1349, English philosopher and logician)
Topliss J G and Edwards R P 1979 J. Med. Chem. 22 1238
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Chattaraj, P.K., Roy, D.R., Giri, S. et al. An atom counting and electrophilicity based QSTR approach. J Chem Sci 119, 475–488 (2007). https://doi.org/10.1007/s12039-007-0061-1
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DOI: https://doi.org/10.1007/s12039-007-0061-1